Alzheimers Res Ther. 2025 Apr 25;17(1):92. doi: 10.1186/s13195-025-01735-5.

ABSTRACT

A recent paper published a lecanemab analysis with data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. While the authors mention the limitations of FAERS, such as "voluntary (underreporting), the inability to establish causality, reporting bias, data quality issues, and the absence of a denominator, which precludes calculating incidence rates", they proceed with generalizations, clinical conclusions, and even treatment recommendations based on the crude disproportionality analysis. Consideration of post-marketing safety reports, including those found in the FAERS database, is an essential component of pharmacovigilance. However, FDA guidance [2, 3] highlights that: (1) "Rates of occurrence cannot be established with reports," (2) "Documenting one or more of these outcomes in a report does not necessarily mean that the suspect product(s) named in the report was the cause of the outcomes," and (3) "Importantly, the FAERS data by themselves are not an indicator of the safety profile of the drug." The FAERS database includes reports from many sources, including reports by companies, as well as from health care professionals and consumers. The reports in the FDA database have significant limitations, including submission of incomplete, inaccurate, untimely, duplicate, relatedness to drug uncertainty, and/or unverified information. Therefore, broader generalizations, clinical conclusions, and treatment recommendations should not be made based solely on FAERS databases analyses.

PMID:40281605 | DOI:10.1186/s13195-025-01735-5

Infect Dis Rep. 2025 Apr 3;17(2):28. doi: 10.3390/idr17020028.

ABSTRACT

BACKGROUND: Interstitial lung diseases (ILDs) are a heterogeneous group of conditions that can cause fibrosis of the lung interstitium, resulting in respiratory failure and death. Patients with an ILD, particularly idiopathic pulmonary fibrosis (IPF) or connective tissue disease-associated ILDs (CTD-ILDs), are prone to develop chronic pulmonary infections such as tuberculosis (TB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD).

METHODS: This case series examines the management of three ILD patients with a usual interstitial pneumonia (UIP) pattern and concomitant NTM-PD or TB at National Institute for Infectious Diseases "Lazzaro Spallanzani" in Rome, Italy, over three years (2019-2022).

RESULTS AND CONCLUSIONS: Multi-disciplinary discussion (MDD) was crucial to define the therapeutic approach due to the increased risk of side effects and drug interactions. Our work underscored how a comprehensive diagnostic evaluation, enriched by MDD, is useful for optimizing the management and reducing drug-related adverse effects and interactions in ILD patients with cavitary lesions.

PMID:40277955 | DOI:10.3390/idr17020028

J Eval Clin Pract. 2025 Apr;31(3):e70110. doi: 10.1111/jep.70110.

ABSTRACT

RATIONALE: Patient safety has become a major concern in healthcare today as 5%-10% of patients experience serious adverse events (SAE) during their hospital stay. The causal assessment of SAE is the responsibility of healthcare professionals (HCP), who use their judgment or a standardize tool. Whether those two methods are replicable to provide similar results remains unclear.

OBJECTIVE: Our aim was to evaluate if causality assessment performed by HCP is replicable when systematically assessed with the Naranjo tool and to validate its performance in Canadian clinical context.

METHODS: We performed pilot retrospective cohort study which included patients with SAE admitted to a Quebec hospital in 2021. Twelve SAE were randomly selected, and two reviewers independently assessed their causality using Naranjo tool. Inter-rater reliability among two reviewers and between HCP was evaluated. Along with criterion validity, sensitivity and specificity were calculated for validation study.

RESULTS: Weighted kappa was 0.92 (good inter-rater reliability) where kappa was 0.84 (good agreement between reviewers). No causality assessment by HCP was documented leading to impossibility in computing replicability. The Naranjo tool showed positive monotonic correlation with expert opinion resulting in rs = 0.208 (p < 0.001). Classification of Naranjo scores to binary variables resulted in sensitivity of 1.00 and specificity of 0.31.

CONCLUSION: Our study suggested that Naranjo tool is reliable and valid to be used in a clinical setting and was able to classify all drug products involved in the occurrence of SAE. Larger scale studies need to be conducted in real-time clinical settings to investigate its performance and utility.

PMID:40275458 | DOI:10.1111/jep.70110

J Biochem Mol Toxicol. 2025 May;39(5):e70280. doi: 10.1002/jbt.70280.

ABSTRACT

The toxicity of chemicals and drugs is a common crisis worldwide. Therefore, the search for protective compounds is growing. Natural compounds such as indole-3-carbinol (I3C) derived from cruciferous vegetables are preferred since they are safe for humans and the environment. This review focuses on I3C potential role in preventing and repairing damage caused by chemicals and drugs. Interestingly, I3C ameliorates hepatotoxicity induced by carbon tetrachloride (CCl4), diethylnitrosamine (DENA), alcohol, gold nanoparticles, and microbial toxins. Additionally, it inhibits carcinogenesis induced by different chemicals and prevents the deleterious effects of different antineoplastic drugs including cisplatin, doxorubicin (DOX), and trabectidin on normal tissues. Moreover, it reduces fetal malformation and protects against micronuclei formation and calstogenecity induced by cyclophosphamide (CP) in bone marrow cells. It also attenuates methotrexate (MTX)-induced hepatotoxicity, mitigates neurotoxicity caused by thioacetamide and clonidine, and protects against aspirin side effects in gastric mucosa. Furthermore, its nanoparticles inhibit neuronal damage caused by glutamate and rotenone. Thus, I3C prevents the toxicities caused by chemicals in the surrounding environment as well as those of consumed drugs.

PMID:40269607 | DOI:10.1002/jbt.70280

Eur J Hosp Pharm. 2025 Apr 24:ejhpharm-2025-004492. doi: 10.1136/ejhpharm-2025-004492. Online ahead of print.

ABSTRACT

INTRODUCTION: Fluid overload is associated with increased morbidity in patients in paediatric intensive care units (PICUs). This study aimed to evaluate pharmaceutical infusion management as a quality assurance measure to reduce fluid overload in routine paediatric intensive care.

METHODS: This was a retrospective observational study in a PICU with two periods: a control period and a period after the implementation of pharmaceutical infusion management (PharmInfuManagement period). Pharmaceutical infusion management consisted of two components carried out simultaneously: the creation of flushing schedules to reduce incompatibilities and flushing volume and the reduction of dilution volume for six non-continuous intravenous (IV) drugs to reduce fluid intake because of IV drugs. The primary outcome was the number of patients with ≥5% fluid overload. In addition, daily furosemide dose (mg/kg/day), non-continuous IV drug volume (mL/kg/day), flushing volume (mL/kg/day) and number of incompatibilities were evaluated.

RESULTS: Sixty-six patients were included in each period. Fluid overload of ≥5% occurred in 52% of patients in the control period and in 29% of patients in the PharmInfuManagement period (p=0.01). Flushing volume decreased from 0.7 mL/kg/day (median Q25/Q75 0.4/1.4) to 0.3 mL/kg/day (median Q25/Q75 0.1/0.7) (p<0.001) after implementation. During the PharmInfuManagement period, potentially incompatible drug combinations were reduced from 17.1% (86/504) to 8.2% (43/523) (p<0.001). The volume required for reconstitution and dilution of non-continuously administered IV drugs was reduced from 8.8 mL/kg/day (median Q25/Q75 7.1/12.6) to 6.8 mL/kg/day (median Q25/Q75 5.5/8.0) (p=0.02).

CONCLUSION: Pharmaceutical infusion management reduces incompatibilities and fluid overload in PICU patients.

PMID:40274396 | DOI:10.1136/ejhpharm-2025-004492

BMJ Glob Health. 2025 Apr 24;10(4):e016720. doi: 10.1136/bmjgh-2024-016720.

ABSTRACT

INTRODUCTION: Plasmodium vivax recurrence prevention using tafenoquine or primaquine is critical for achieving Thailand's malaria elimination targets. Both drugs may cause haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. This study evaluated the operational feasibility and safety of administering tafenoquine or primaquine after quantitative G6PD point-of-care testing in Thailand.

METHODS: This prospective, observational, multicentre, longitudinal study was conducted between 23 May 2022 and 14 September 2023 during pilot implementation at seven sites in Yala and Mae Hong Son provinces. Eligible patients were ≥16 years old with uncomplicated P. vivax malaria. G6PD enzyme activity was quantified using a point-of-care device. All patients received 3-day chloroquine plus (based on G6PD enzyme activity): single-dose tafenoquine 300 mg (≥6.1 U/g Hb), or primaquine 15 mg/day for 14 days (≥4.1 U/g Hb), or primaquine 45 mg/week for 8 weeks (≤4.0 U/g Hb), with follow-up on days 5 and 14. Hospital admissions were reviewed to confirm acute haemolytic anaemia cases. The primary endpoint was the percentage of P. vivax patients ≥16 years old treated or not treated with tafenoquine in accordance with G6PD enzyme activity.

RESULTS: Of 316 P. vivax patients screened, 187 were enrolled. All patients completed quantitative G6PD testing. According to G6PD status, appropriate use or non-use was 100% (95% CI 97.2, 100 (132/132)) with tafenoquine, 100% (95% CI 96.5, 100 (104/104)) with daily primaquine and 99.5% (97.1, 100 (186/187)) with weekly primaquine. At day 5, adverse events possibly related to haemolysis occurred in 46.3% (37/80) of patients with tafenoquine, 56.8% (46/81) with daily primaquine and 77.8% (14/18) with weekly primaquine, with no confirmed drug-induced acute haemolytic anaemia cases.

CONCLUSION: Point-of-care quantitative G6PD testing prior to appropriate tafenoquine or primaquine administration was operationally feasible within the Thailand health system, with no concerning adverse events, supporting implementation of this treatment algorithm in areas of active P. vivax transmission.

PMID:40274286 | DOI:10.1136/bmjgh-2024-016720

Future Oncol. 2025 Apr 24:1-11. doi: 10.1080/14796694.2025.2495543. Online ahead of print.

ABSTRACT

AIM: The present study assessed the incidence of drug-induced interstitial lung disease (ILD) recurrence among breast cancer patients who underwent rechallenge with cancer-directed therapy.

MATERIALS & METHODS: Japanese insurance claims data and the Diagnosis Procedure Combination database (2009-2022) involving 81,601 patients were analyzed to evaluate 1,042 breast cancer patients who developed ILD. Of these, 566 patients underwent cancer-directed therapy rechallenge, and 42.1% of them were re-challenged with the same therapeutic regimen that caused the initial ILD.

RESULTS: ILD recurrence was observed in 18.9% of the patients, with a median recurrence time of 40 days. The drugs most commonly causing ILD were cytotoxic agents, and those most frequently used for rechallenge were cytotoxic agents.

CONCLUSION: A notable ILD recurrence rate was observed in breast cancer patients after a cancer-directed therapy rechallenge, highlighting the need for cautious treatment planning and personalised strategies to balance cancer control while mitigating ILD risk.

PMID:40272014 | DOI:10.1080/14796694.2025.2495543

Toxicol Rep. 2025 Apr 5;14:102021. doi: 10.1016/j.toxrep.2025.102021. eCollection 2025 Jun.

ABSTRACT

Immunotherapy has revolutionized cancer treatment, offering significant survival superiority for advanced malignancies. However, immunotherapy is associated with various immune-related adverse events, one of the most common of them being dermatologic toxicities. Previous studies have reported dermatologic adverse events in almost half of the cancer patients undergoing immunotherapy. The spectrum of dermatologic toxicities ranges from mild, self-limiting reactions to severe, life-threatening conditions, and includes maculopapular rash, pruritus, vitiligo-like depigmentation, psoriasiform eruption, lichenoid eruption, bullae, photosensitivity, hair loss, nail changes, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The management strategies are based on personalized treatment plans, multidisciplinary approaches, and timely therapeutic interventions aimed at addressing dermatologic toxicities while preserving immunotherapy efficacy. Based on the latest findings, this paper offers a novel perspective and provides an evidence-based review of the pathogenesis, manifestations, incidence, grading, clinical management, and prognostic significance of these toxicities, underlining the importance of balancing the efficacy of immunotherapy with timely and proactive management of their dermatological toxicities to enhance patient outcomes and quality of life.

PMID:40271531 | PMC:PMC12017974 | DOI:10.1016/j.toxrep.2025.102021

J Cardiol Cases. 2024 Nov 7;31(2):42-45. doi: 10.1016/j.jccase.2024.10.001. eCollection 2025 Feb.

ABSTRACT

Pemafibrate is a selective peroxisome proliferator-activated receptor alpha (PPARα) activator. Pemafibrate has been shown to reduce serum triglyceride levels to an equivalent or greater extent than traditional fibrates, with a lower incidence of drug-related adverse events. Pemafibrate may have the potential to improve clinical outcomes in carefully selected patients with cardiovascular diseases by ameliorating dyslipidemia and stabilizing systemic arteriosclerosis. Additionally, several experimental studies have demonstrated a novel potential for pemafibrate in improving heart failure through its pleiotropic effects. We encountered two patients with systolic heart failure that was refractory to guideline-directed medical therapy. Both patients experienced further cardiac reverse remodeling and an improvement in hypertriglyceridemia following a six-month course of pemafibrate add-on therapy. Pemafibrate might facilitate cardiac reverse remodeling when incorporated into conventional heart failure medications. Further prospective randomized controlled studies are warranted to evaluate the clinical implications of incorporating pemafibrate into medical therapy for heart failure patients. Future research should also explore the long-term effects of pemafibrate on cardiovascular outcomes, the underlying mechanisms of its pleiotropic benefits, and its efficacy in diverse patient populations to solidify its role in heart failure management.

LEARNING OBJECTIVE: Pemafibrate, a recently introduced selective peroxisome proliferator-activated receptor alpha activator that improves hypertriglyceridemia, may facilitate cardiac reverse remodeling when incorporated into conventional heart failure medications.

PMID:40270895 | PMC:PMC12013756 | DOI:10.1016/j.jccase.2024.10.001

J Biol Rhythms. 2025 Apr 23:7487304251326628. doi: 10.1177/07487304251326628. Online ahead of print.

ABSTRACT

Circadian clocks regulate many aspects of human physiology, including cardiovascular function and drug metabolism. Administering drugs at optimal times of the day may enhance effectiveness and reduce side effects. Certain cardiac antiarrhythmic drugs have been withdrawn from the market due to unexpected proarrhythmic effects such as fatal Torsade de Pointes (TdP) ventricular tachycardia. The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a recent global initiative to create guidelines for the assessment of drug-induced arrhythmias that recommends a central role for computational modeling of ion channels and in silico evaluation of compounds for TdP risk. We simulated circadian regulation of cardiac excitability and explored how dosing time of day affects TdP risk for 11 drugs previously classified into risk categories by CiPA. The model predicts that a high-risk drug taken at the most optimal time of day may actually be safer than a low-risk drug taken at the least optimal time of day. Based on these proof-of-concept results, we advocate for the incorporation of circadian clock modeling into the CiPA paradigm for assessing drug-induced TdP risk. Since cardiotoxicity is the leading cause of drug discontinuation, modeling cardiac-related chronopharmacology has significant potential to improve therapeutic outcomes.

PMID:40269490 | DOI:10.1177/07487304251326628

J Autoimmun. 2025 May;153:103423. doi: 10.1016/j.jaut.2025.103423. Epub 2025 Apr 22.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for cancer. However, frequent and sometimes life-threatening immune-related adverse events (irAEs) are associated with ICI treatment. Therefore, it is imperative to establish a model for predicting the risk of irAEs to identify high-risk groups, enable more accurate clinical risk‒benefit analysis for ICI treatment and decrease the incidence of irAEs. However, no ideal model for predicting irAEs has been applied in clinical practice. The aim of this study was to analyze the systemic immune characteristics of patients with irAEs and establish a model for predicting the risk of irAEs.

METHODS: We conducted a study to monitor irAEs in patients with advanced breast cancer undergoing immunotherapy during and following the treatment course. Peripheral blood mononuclear cells (PBMCs) were collected before and after two cycles of therapy. Mass cytometry time-of-flight (CyTOF) was employed to identify baseline and posttreatment immune cell subpopulations, and the relationships between the proportions of cells in these subpopulations and the occurrence of irAEs were explored. Additionally, we conducted subgroup analyses stratified by the anatomic location and time of onset of irAEs. Furthermore, we developed a logistic regression model to predict the risk of irAEs and validated this model using two independent validation cohorts from the Gene Expression Omnibus (GEO) database (accession numbers GSE189125 and GSE186143).

RESULTS: By analyzing 106 blood samples and samples from two independent validation cohorts (n = 16 and 60 patients), we found that high proportions of CXCR3+CCR6+CD4+ T cells and CD38+CD86+CXCR3+CCR6+CD8+ T cells and a low proportion of CXCR3lowCD56dim natural killer (NK) cells at baseline were significantly correlated with the incidence of irAEs (P = 0.0029, P < 0.001, and P = 0.0017, respectively). In the subgroup analysis, we observed consistent results in patients with immune-related pneumonitis (ir-pneumonitis) and immune-related thyroiditis (ir-thyroiditis). In the early irAE group, the baseline proportion of CXCR3+CCR6+CD4+ T cells was greater than that in the late irAE group (P = 0.011). An analysis of PBMCs before and after ICI treatment revealed thatthe dynamic changes in the proportions of naïve CD4+ T cells and CXCR3lowCD56dim NK cells were closely related to irAE occurrence. Finally, we ultimately developed a model for predicting the risk of irAEs, which yielded an area under the receiver operating characteristic curve (AUROC) of 0.79 in the training cohort and an AUROC of 0.75 in the single-cell validation cohort (GSE189125).

CONCLUSIONS: These findings indicate that different populations of immune cells are associated with different irAEs and that characterization of these cells may be used as biomarkers to predict the risk of specific toxicities. This will facilitate the management of irAEs and may lead to a reduction in the incidence of irAEs.

PMID:40267835 | DOI:10.1016/j.jaut.2025.103423

Immunotherapy. 2025 Apr;17(5):339-346. doi: 10.1080/1750743X.2025.2492541. Epub 2025 Apr 23.

ABSTRACT

AIMS: Immune-related adverse events (irAEs) are common side effects of immune checkpoint inhibitor (ICI) cancer therapy, affecting approximately half of ICI-treated patients. irAEs may be severe and result in hospitalization. This study examined the risk factors and outcomes of irAE-related hospitalization.

METHODS: We conducted a retrospective study including 202 metastatic cancer patients treated with ICIs at Kuopio University Hospital, Finland, in 2015-2022.

RESULTS: IrAEs occurred in 57.4% of the patients. About 26.0% of them required inpatient treatment. Hospitalization was associated with severe (grades III - IV) toxicities and need for systemic corticosteroids. Median overall survival (mOS) for hospitalized patients was 12.9 months and for outpatients with irAEs 26.9 months (p = 0.006). The duration of ICI therapy was 1.8 months in hospitalized patients and 5.0 months in outpatients (p < 0.001). The median maximum glucocorticoid doses were 52 mg and 100 mg, respectively (p < 0.001).

CONCLUSIONS: IrAE-related hospitalization deteriorated the survival of ICI-treated patients, likely due to decreased biological efficacy of ICIs resulting from short therapy periods and strong immunosuppression by glucocorticoids.

PMID:40264419 | DOI:10.1080/1750743X.2025.2492541

BMJ Evid Based Med. 2025 Apr 23:bmjebm-2024-113497. doi: 10.1136/bmjebm-2024-113497. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the patient-reported outcomes (PROs) and acupuncture-related adverse events (A-AEs) in acupuncture randomised controlled trials (RCTs).

DESIGN: Cross-sectional meta-epidemiological study.

DATA SOURCES: We comprehensively searched for eligible studies between 1 January 2014 and 1 May 2024, in MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang Data and VIP Database.

ELIGIBILITY CRITERIA: RCTs that used acupuncture as the intervention group to obtain the efficacy and/or safety of acupuncture therapy. Acupuncture therapy should be based on Traditional Medicine theory.

MAIN OUTCOME MEASURES: We assessed (1) the general characteristics of acupuncture RCTs; (2) the general characteristics of PROs; (3) the reporting scores of PROs by the Extension of Consolidated Standards of Reporting Trials of Patient-Reported Outcomes (CONSORT PRO Extension); (4) the general characteristic of A-AEs; (5) the incidence of A-AEs.

RESULTS: We included 476 studies in this study. 296 (62.2%) used PROs as study outcomes, 272 (57.1%) reported safety outcomes. The Visual Analogue Scale (149, 23.7%) and the Pittsburgh Sleep Quality Index (42, 6.7%) were the most common PROs reported. The reporting of PROs was incomplete, with sufficiently reporting scores ranging from 2.7% to 97.6% across the CONSORT PRO Extension. 164 studies reported A-AEs, of which 141 reported specific details, and we found that the OR for the incidence of AEs in the acupuncture group compared to the control group was 1.434 (95% CI 1.148 to 1.793). We identified 1277 reports of A-AEs in eligible studies, predominantly tissue injury (eg, haematoma, bleeding), irritation (eg, pain, post-acupuncture discomfort), with no reports of serious A-AEs. The reporting of A-AEs lacked details on the acquisition methods (15.5%), occurrence time (5.5%), A-AEs' treatment (18.1%) and A-AEs' recovery (19.7%). Studies that reported funding, registry information, acupuncturist qualifications and non-significant primary outcomes were associated with the A-AEs' reporting, and the difference was statistically significant (p≤0.05).

CONCLUSION: This study found that the reporting of PROs and A-AEs was insufficient in acupuncture RCTs. Future studies should clarify the clinical significance of using PROs as outcomes and report AEs comprehensively to provide patients with sufficient information on the benefits and harms of acupuncture treatments.

PMID:40268340 | DOI:10.1136/bmjebm-2024-113497

JAMA. 2025 Apr 23. doi: 10.1001/jama.2025.3810. Online ahead of print.

ABSTRACT

IMPORTANCE: Electronic cigarette use (vaping) among adolescents and young adults is common. Few treatments have been tested in this population.

OBJECTIVE: To evaluate the efficacy of varenicline for nicotine vaping cessation in youth who do not smoke tobacco regularly.

DESIGN, SETTING, AND PARTICIPANTS: A 3-group randomized clinical trial compared 12 weeks of double-blind varenicline vs placebo, each added to brief, remotely delivered behavioral counseling and compared with single-blind enhanced usual care, with monthly follow-up to 24 weeks. The trial was conducted among youth, aged 16 to 25 years, who vaped nicotine daily or near daily, did not regularly smoke tobacco, and wanted to reduce or quit vaping, in a single US state from June 2022 to May 2024. Data collection ended May 28, 2024.

INTERVENTIONS: Participants were randomized (1:1:1) to 12 weeks of varenicline titrated to 1 mg twice daily over 7 days (standard titration), weekly counseling, and referral to text messaging vaping cessation support (This is Quitting [TIQ]) (n = 88); identical placebo, weekly counseling, and referral to TIQ (n = 87); or enhanced usual care (referral to TIQ only) (n = 86).

MAIN OUTCOMES AND MEASURES: Biochemically verified continuous vaping abstinence for the last 4 weeks of varenicline treatment vs placebo (primary outcome). Secondary outcomes included bioverified continuous abstinence from weeks 9 through 24 in the varenicline and placebo groups. Additional analyses compared varenicline group and placebo group with enhanced usual care.

RESULTS: Of 261 randomized participants (mean age, 21.4 years; 53% female), 254 completed the trial (97.3%). For varenicline and placebo, continuous abstinence rates were 51% vs 14% during weeks 9 through 12 (adjusted odds ratio [aOR], 6.5 [95% CI, 3.0-14.1]; P < .001) and 28% vs 7% during weeks 9 through 24 (aOR, 6.0 [95% CI, 2.1-16.9]; P < .001). Varenicline had higher continuous abstinence rates vs enhanced usual care during weeks 9 through 12 (51% vs 6%; aOR, 16.9 [95% CI, 6.2-46.3]) and during weeks 9 through 24 (28% vs 4%; aOR, 11.0 [95% CI, 3.1-38.8]). Continuous abstinence rates were not significantly different between the placebo and enhanced usual care groups. Study medication was generally well tolerated. Two varenicline participants (2%) and 1 placebo participant (1%) discontinued study medications due to adverse events. No drug-related serious adverse events occurred. Treatment-emergent adverse events were reported by 76 (86%) in the varenicline group, 68 (79%) in the placebo group, and 68 (79%) in the enhanced usual care group.

CONCLUSIONS AND RELEVANCE: Varenicline, combined with behavioral counseling, increased vaping abstinence in youth who vape nicotine and do not regularly smoke tobacco.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05367492.

PMID:40266580 | DOI:10.1001/jama.2025.3810

J Nurs Adm. 2025 May 1;55(5):267-273. doi: 10.1097/NNA.0000000000001574.

ABSTRACT

OBJECTIVE: This study aimed to identify predictors of adverse drug reaction (ADR) monitoring practices among hospital nurses.

BACKGROUND: ADR monitoring is crucial for patient safety but remains insufficient in healthcare institutions.

METHODS: A cross-sectional descriptive study was conducted with 165 RNs from 4 tertiary hospitals. Data were collected using self-report questionnaires between August 5 and September 16, 2022.

RESULTS: Regression analysis revealed significant associations between ADR monitoring practices and nurses' attitudes, workload intensity, and work units. Of the nurses, 61.2% observed ADRs in the past year, and 31.5% had received ADR education. However, only 51.5% reported all ADR cases. Major barriers to reporting included time constraints and insufficient knowledge.

CONCLUSION: The findings highlight the need for educational programs to enhance nurses' knowledge and attitudes toward ADRs and the importance of strategies to support nursing units and reduce workload intensity to ensure safe medication administration.

PMID:40266099 | DOI:10.1097/NNA.0000000000001574

BMC Pharmacol Toxicol. 2025 Apr 22;26(1):91. doi: 10.1186/s40360-025-00920-4.

ABSTRACT

BACKGROUND: Ganirelix, a third-generation GnRH antagonist, is widely used in assisted reproductive technology (ART) for rapid pituitary suppression to prevent premature luteinizing hormone (LH) surges. Despite its extensive clinical use, real-world evidence on its safety in large populations remains scarce. This study aimed to evaluate the safety profile of ganirelix by comprehensively analyzing adverse drug events (ADEs) using real-world data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japan Adverse Drug Event Reporting (JADER) database.

METHODS: We extracted ADE data from FAERS (Q1 2004-Q2 2024) and JADER (Q1 2009-Q1 2024). Disproportionality analyses, including reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian Confidence Propagation Neural Networks (BCPNN), and Multi-item Gamma Poisson Shrinkage (MGPS), were employed to identify significant associations between ganirelix and ADEs.

RESULTS: In the FAERS database, we identified 1,096 ganirelix-related ADE reports, spanning 26 system organ classes (SOCs). A total of 65 positive signals were detected, including ADEs consistent with drug label such as ovarian hyperstimulation syndrome (OHSS) (n = 290, ROR 2462.76, PRR 2168.48, EBGM05 1655.59, IC025 9.18), injection site pain (n = 54, ROR 3.99, PRR 3.93, EBGM05 3.13, IC025 0.31), and fetal death (n = 6, ROR 21.05, PRR 21.00, EBGM05 10.72, IC025 2.72). Additionally, unexpected signals not listed in the drug label were identified, including ectopic pregnancy (n = 7, ROR 33.02, PRR 32.93, EBGM05 17.64, IC025 3.37), maternal exposure before pregnancy (n = 30, ROR 76.09, PRR 75.16, EBGM05 74.72, IC025 6.22), dermatitis allergic (n = 4, ROR 7.98, PRR 7.97, EBGM05 3.50, IC025 1.33), and bladder tamponade (n = 4, ROR 771.47, PRR 770.3, EBGM05 311.57, IC025 7.80). The median time to ADE onset was 13 days. External validation using the JADER database (62 ganirelix-related ADE reports) confirmed four signals, including abortion (n = 19), OHSS (n = 17), missed abortion (n = 9), and fetal death (n = 8), aligning with FAERS findings.

CONCLUSION: This study provides a robust real-world safety evaluation of ganirelix, with findings corroborated by two independent pharmacovigilance databases. While consistent with clinical observations, the identification of unexpected signals warrants further pharmacoepidemiological investigations to confirm these results.

PMID:40264185 | DOI:10.1186/s40360-025-00920-4

Front Immunol. 2025 Apr 8;16:1582050. doi: 10.3389/fimmu.2025.1582050. eCollection 2025.

ABSTRACT

OBJECTIVE: Advanced cervical cancer remains associated with high mortality rates. While pembrolizumab has improved clinical outcomes in cervical cancer, the therapeutic efficacy in advanced stages is often compromised by immune-related adverse events (irAEs). This study aimed to systematically analyze pembrolizumab-associated adverse events (AEs) in cervical cancer using the FDA Adverse Event Reporting System (FAERS) database, providing new insights for optimizing clinical practice.

METHODS: AE reports related to pembrolizumab in cervical cancer were extracted from the FAERS database (Q1 2016 to Q4 2024). Disproportionality analyses were performed using multiple algorithms, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). AEs were classified by system organ class (SOC) and preferred term (PT) based on the Medical Dictionary for Regulatory Activities (MedDRA), then ranked by frequency and signal strength.

RESULTS: A total of 646 pembrolizumab-related AE reports in cervical cancer were identified. Age distribution peaked at 45-65 years cohort (32.75%), followed by 18-44 years (12.85%), 66-75 years (11.76%), and >75 years (4.64%). Among 270 AE reports with documented onset timelines, events predominantly occurred 3-6 months after pembrolizumab initiation (n=114, 41.36%). Clinical outcomes were categorized as other (52.80%), hospitalization (27.00%), death (10.25%), unknown (6.06%), life-threatening (2.77%), and disability (1.12%). Predominant AEs involved hematologic, endocrine, dermatologic, neurologic, gastrointestinal, urinary, and reproductive systems.

CONCLUSION: This real-world pharmacovigilance study systematically characterizes pembrolizumab-associated AEs in cervical cancer, identifying high-signal events such as hematologic disorders, endocrine dysfunction, and dermatologic toxicities. These findings provide critical evidence for risk stratification and safety monitoring in clinical practice, emphasizing the need for organ-specific vigilance during the 3-6 months treatment window.

PMID:40264768 | PMC:PMC12011867 | DOI:10.3389/fimmu.2025.1582050

Acta Med Indones. 2025 Jan;57(1):74-80.

ABSTRACT

BACKGROUND: Geriatric patients are often subject to polypharmacy, increasing their risk of adverse drug reactions (ADRs). This study evaluated polypharmacy practices, ADR incidence, predictive factors, and the applicability of the GerontoNet Score at a tertiary referral teaching hospital in Indonesia.

METHODS: This retrospective study included 340 geriatric inpatients at Dr. Cipto Mangunkusumo Hospital, Jakarta, in 2023. The relationship between demographic data, comorbidities, number of drugs used, and ADR events was analyzed using the Chi-square test. The association between GerontoNet ADR scores and ADR events was also assessed.

RESULTS: The study included 182 (53.5%) male and 158 (46.5%) female patients, with a mean age of 71.9±6.1 years. Of these, 70.9% were aged 65 to 74. A total of 78.8% of patients had ≥ 4 comorbidities. The number of drugs ranged from 3 to 28, with a mean of 10.7 drugs and a median of 10 drugs. ADRs were detected in 26 patients (7.6%), with 17 cases in females and 9 in males (p=0.044). Insulin- and diuretic-induced hypokalemia were the most frequent ADR (13 patients), followed by heparin-induced thrombocytopenia (3 patients). No significant correlation was found between ADRs and age (p=0.505), number of comorbidities (p=0.425), number of drugs (p=0.576), or GerontoNet ADR Score (p=0.530).

CONCLUSION: Polypharmacy is prevalent at Dr. Cipto Mangunkusumo Hospital, yet the incidence of ADRs is relatively low. Most ADRs were related to high-alert drugs, while no significant correlations were found between age, polypharmacy, comorbidities, or GerontoNet Score with ADR events.

PMID:40263686

Clin Cancer Res. 2025 Apr 21. doi: 10.1158/1078-0432.CCR-25-0206. Online ahead of print.

ABSTRACT

PURPOSE: Izalontamab (SI-B001) is a novel EGFR×HER3 bispecific antibody. This first-in-human phase I study presents the safety and pharmacokinetics of izalontamab.

PATIENTS AND METHODS: Previously treated patients with locally advanced or metastatic epithelial tumors were enrolled in the dose-escalation or dose-expansion phases. The dose-escalation phase consisted of an accelerated titration and a "3+3" design with 9 dose levels from 0.4 to 28.0 mg/kg. The dose-expansion phase included 5 dose levels from 6.0 to 21.0 mg/kg. Izalontamab was administered intravenously weekly(QW) or every two weeks(Q2W) in a four-week cycle. Available pre-treatment specimens were obtained to explore the relationship between EGFR/HER3 expression and efficacy.

RESULTS: 60 patients were enrolled. Among the 60 enrolled patients, 49 had non-small cell lung cancer(NSCLC), 6 had nasopharyngeal cancer, 3 had head and neck cancer(HNSCC), and 2 had other types of cancer. The most common treatment-related adverse events were rash (42%), paronychia (25%) and infusion-related reactions (23%). No drug-related death occurred. Izalontamab displayed non-linear pharmacokinetic behavior and clearance at steady state appeared to be approaching a dose-independent value at 6 mg/kg and above. The best response included 2 confirmed partial responses in NSCLC and HNSCC patients; 18 patients had stable disease, including NSCLC(n = 17) and colorectal cancer(n=1). The recommended phase 2 dose for izalontamab was determined as 9-16mg/kg QW weekly.

CONCLUSIONS: Izalontamab was well tolerated and demonstrated preliminary antitumor activity in patients with locally advanced or metastatic epithelial tumors, supporting it as a promising therapeutic candidate for combination therapies, with a phase 3 study currently underway.

PMID:40260627 | DOI:10.1158/1078-0432.CCR-25-0206

Oral Dis. 2025 Apr 21. doi: 10.1111/odi.15337. Online ahead of print.

ABSTRACT

OBJECTIVE: Neuropsychiatric disorders are associated with poor oral health, with antipsychotics as potential contributors. This study aimed to analyse the oral adverse effects of antipsychotics using the EudraVigilance database.

METHODS: A case/noncase analysis was conducted to calculate reporting odds ratios (ROR) and assess the disproportionality of oral adverse events.

RESULTS: A total of 5663 reports of oral adverse effects related to antipsychotics were identified. Atypical antipsychotics had a higher overall incidence (5663 vs. 787 for typical), but typical antipsychotics showed stronger associations with specific oral issues (ROR = 2.2 vs. 1.6 for atypical). The most commonly reported effects were disturbances in salivary flow, including xerostomia and hypersalivation. Olanzapine and quetiapine were linked to dry mouth (ROR = 1.8 and 3.0) and tooth loss (ROR = 1.7 and 1.8). Clozapine had the highest number of reports (1619) and ROR (33.1) for hypersalivation. Disproportionality analysis revealed significant associations with orofacial dyskinesia for all antipsychotics, except clozapine. Aripiprazole had the highest ROR (13.7) for orofacial dyskinesia and was linked to a swollen tongue in patients aged ≤ 17 years (12 cases, ROR = 3.6). No sex-based differences were identified.

CONCLUSIONS: Antipsychotics significantly affect oral health, highlighting the need for preventive dental care and interventions to reduce these effects and improve patient well-being.

PMID:40259575 | DOI:10.1111/odi.15337